Cardiopoietic stem cell therapy in ischaemic heart failure: long-term clinical outcomes.
Cardiopoiesis
Clinical trial
Heart failure
Longitudinal
Regenerative medicine
Stem cell
Journal
ESC heart failure
ISSN: 2055-5822
Titre abrégé: ESC Heart Fail
Pays: England
ID NLM: 101669191
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
revised:
01
09
2020
received:
03
07
2020
accepted:
09
09
2020
pubmed:
24
10
2020
medline:
24
10
2020
entrez:
23
10
2020
Statut:
ppublish
Résumé
This study aims to explore long-term clinical outcomes of cardiopoiesis-guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial. CHART-1 is a multinational, randomized, and double-blind trial conducted in 39 centres in heart failure patients (n = 315) on standard-of-care therapy. The 'active' group received cardiopoietic stem cells delivered intramyocardially using a retention-enhanced catheter. The 'control' group underwent patient-level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann-Whitney estimator 0.52, 95% confidence interval (CI) 0.45-0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow-up, patients with left ventricular end-diastolic volume of 200-370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16-0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09-0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years. Longitudinal follow-up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long-term clinical follow-up thus offers guidance for future targeted trials.
Identifiants
pubmed: 33094909
doi: 10.1002/ehf2.13031
pmc: PMC7754898
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3345-3354Subventions
Organisme : NCI NIH HHS
ID : R01 CA204481
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA206026
Pays : United States
Informations de copyright
© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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